Candidate: The applicant is a veterinarian who holds a Ph.D. in immunology. She was trained at Cornell University, and her thesis research focused on innate immunity during protozoal infection. For the past two years, she has studied immunity to helminths in the laboratory of Dr. Judith Appleton. She is seeking to develop new scientific directions in the area of immune regulation in parasitic disease. Her long term career goal is to develop an independent academic career. Research Proposal: The liver is an important site of infectious, autoimmune, and malignant diseases. Hepatic immune responses and their regulation are critical to the outcome of these disorders. Dendritic cells indisputably play key roles in the induction and regulation of immunity. Their attributes and potential regulatory functions are the subjects of this proposal. We have found that IL-10 knockout mice infected orally with the parasite, Trichinella spiralis, develop severe necrotizing hepatitis while C57BL/6 mice do not. Hepatic injury develops very rapidly, within hours after release of the migratory form of the parasite in the intestine. Our data suggest that the parasite induces an immune response in the intestine that protects the liver against damage caused by migratory larvae. We will investigate the role of dendritic cells in this regulatory process. The goals of this project are to define the source of IL-10 in the liver during infection, determine how IL-10 influences dendritic cell phenotype and function, and understand the mechanism of tolerance induced (i.e., T cell fate). Environment: Mentorship will be shared by Drs. Judith Appleton and Edward Pearce. Both are accomplished investigators, well known for their expertise in immune defense against helminths. Studies will be conducted at the James A. Baker Institute for Animal Health of the College of Veterinary Medicine, Cornell University. The Institute has a strong tradition of training veterinarians for independent research careers. The research emphasis of the Institute is directed towards animal models of disease, providing a highly supportive environment for the applicant's career development.